Recent advances in protein sequence analysis by mass spectroscopy combined with the availability of large protein databases have created unique opportunities in diabetes research. This application requests funds for the acquisition of a Matrix Assisted Laser Desorption Ionization Time-of Flight (MALDI TOF) mass spectrometer to be used for NIH-funded research projects that are currently underway by nine Investigators at the Joslin Diabetes Center. These research projects are relevant to both type 1 and type 2 diabetes, and will be carried out in 5 research sections at the Joslin. These studies address a number of areas of diabetes research, including autoimmunity related to type 1 diabetes, mechanisms of insulin resistance, type 2 diabetes, obesity, metabolism, and vascular complications. The specific instrument requested is the Axima-CFR MALDI TOF manufactured by Kratos Analytical. Features of this system include monoisotopic resolution (>10000 Fwhm), mass accuracy <10 ppm, sensitivity of <10 fmol/mu l, and a unique patented curve field reflectron that enables the generation of seamless post source decay. The primary applications for this mass spectrometer will be to identify changes in protein expression and post-translational modification relevant to diabetes and its vascular complications. Preliminary studies using the Axima-CFR at the University of Massachusetts have demonstrated that this instrument is highly effective for the proposed uses described in this grant. This instrument will be operated and maintained by a Proteomies Core Laboratory, centrally located among research laboratories at the Joslin. Usage of this instrument is estimated as at least 90%, corresponding to approximately 4 hours per week for each of the 9 investigators participating in this grant. Diabetes research has not yet fully benefited from the information available from current mass spectroscopic technologies. The Investigators assembled for this grant have the expertise and research models available, as well as the clear needs, to utilize mass spectroscopic protein analysis for the identification of novel mechanism and targets for the treatment of diabetes and it vascular complications.